L-lysine is the most important essential amino acid as nutrients for human and animal, and plays a very important role in the food industry, breeding industry and feed industry. In recent years, the market demand for L-lysine has steadily increased, and the volume of sales of L-lysine on the world market is more than one million tons. Currently, lysine is mainly produced by microorganism fermentation.
In many microorganisms, L-lysine is synthesized by using aspartic acid as the precursor, including two steps in common with some amino acids, such as methionine and threonine. In E. coil, the biosynthesis pathway for L-lysine includes a nine-step enzymatic process (indicated by the following scheme), wherein the first-step reaction of lysine biosynthesis catalyzed by aspartokinase is the rate-limiting step of lysine production, and the activity of aspartokinase determines the ratio of metabolic flux to L-lysine synthetic pathway. In E. coli, there are 3 aspartokinases, named as aspartokinase I (AK I, encoded by the thrA gene), aspartokinase II (AK II, encoded by the metL gene), aspartokinase III (AK III, encoded by the lysC gene, and the nucleotide sequence of the encoding gene is represented by SEQ ID NO: 1, and the amino acid sequence thereof is represented by SEQ ID NO: 2), respectively. AK I and AK II are both bifunctional enzymes which further possess homoserine dehydrogenase activity. AK I is inhibited by threonine and lysine feedback on the enzyme activity level, and AK III is inhibited by lysine (the final product) feedback on the enzyme activity level (Bearer C F, Neet K E; Stadtman, E R, Cohen, G N, LeBras, G., Robichon-Szulmajster, H. (1961). “Feed-back Inhibition and Repression of Aspartokinase Activity in Escherichia coli and Saccharomyces cerevisiae.” J. Biol. Chem.). AK II is not inhibited by the feedback of amino acids in the aspartate family on the enzyme activity level, but it is strictly regulated on the transcription level (X Dong, P J Quinn, X Wang. (2011). “Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the production of L-threonine. “Biotechnology advances).
